Using a combination of genetics and molecular biology in Drosophila, Hays will study how dynein is targeted to different tissue/cells to perform a variety of functions. He will concentrate on the dynein intermediate and light chains since they have been indicated as having a targeting function. He will generate nulls, analyzing the resulting phenotypes, and will also characterize proteins that interact with the light and intermediate chains. He will carry out studies with dynein mutants to help elucidate the role of dynein in mitosis. These will also involve studies on asymmetric divisions in neuroblasts. In vitro collaborative studies will involve binding of dynein to kinetochores in permeabilized systems. Since dynein binding to cargo appears in many instances to be mediated by dynactin, mutants that modify dynein-dynactin interactions will be characterized. This is a global study of the various motilities that cytoplasmic dynein performs in eukaryotic cells.